The human inherited disorders of sphingolipid metabolism (Gaucher, Krabbe, Farber, Niemann-Pick, etc.) are characterized by severe symptoms, particularly in their infantile forms, which include mental retardation, neurological degeneration, and malfunction of various organs. We hope to produce model forms of the disorders by synthesizing inhibitors of the respective hydrolytic enzymes and administering them to young rats or mice. The resultant changes in brain and other organs will be followed by chemical and enzyme assays, isotope incorporation measurements, and morphological examination. Other compounds will be synthesized that can inhibit the enzymes that synthesize the sphingolipids accumulating in these diseases. The enzymes will be assayed in vitro and promising inhibitors will be administered to normal and to model animals, simultaneously treated with hydrolase inhibitor. It is hoped that synthetase inhibition will block accumulation of the sphingolipids and reverse the symptoms produced by hydrolase inhibition. It is expected that the various inhibitors will clarify the roles of the sphingolipid enzymes in normal and pathological brain function. Some of the compounds made have proved to be inhibitors of monoamine oxidase, type B, and further tests will be made to clarify the problem of drug side reactions in our animals.